Marine natural products are of considerable interest because of their structural novelty, functional diversity and potent biological activity. In particular, marine macrolides are well known for their fascinating molecular structure and potent anticancer activity (see Qi, Y.; Ma, S. Chem Med Chem 2011, 6, 399; and Bhatnagar, I., et al., Mar. Drugs 2010, 8, 2702). Superstolides A (1) and B (2), two marine macrolides, were isolated in minute amounts from the deep-water marine sponge Neosiphonia superstes (see D'Auria, M. V., et al., J Am. Chem. Soc. 1994, 116, 6658; and D'Auria, M. V et al., J. Nat. Prod. 1994, 57, 1595). Their absolute structures were determined by extensive spectroscopic methods. The structural novelty of these two molecules is characterized by a unique 16-membered macrolactone attached to a functionalized cis-decalin.

Both superstolides A and B exhibit potent antiproliferative effect against several tumor cell lines with IC50 values ranging from 4.8 to 64 nM. Their structures are novel and unprecedented, suggesting that they might have a unique cellular target(s) and a novel mechanism of action. Unfortunately, the isolation yields for both superstolides A and B are only 0.003% and 0.0003%, respectively. In addition, the marine sponge Neosiphonia superstes live at 500-515 meters deep in the ocean off New Caledonia, which makes the collection of the sponge very difficult and dangerous. Furthermore, collecting a large amount of marine sponge has the potential to cause significant damage to the marine habitat. Due to the scarcity of these compounds there has not been enough material for further biological investigation, a common problem in the study of biologically active marine natural products. The potent anticancer activities coupled with their challenging molecular structures have attracted a great deal of attention from the synthetic organic chemistry community.
Currently there is a need for novel compounds that can be prepared on a commercial useful scale and that retain the useful pharmacologic properties of superstolide A and B. Such compounds would be useful not only as therapeutic agents for the treatment of cancer, but also as pharmacologic tools for further studying the mechanism of action of superstolide A and B.